Cancer in its different forms is a major cause of death in humans. One-third of all individuals in the United States develop cancer and 20% die from cancer (494,000 in 1988).
The most widely used therapeutic treatments of cancer are surgery, radiation and chemotherapy. In recent years, another therapeutic treatment based on use of biological response modifiers (BRM) has also been proposed. The BRMs used include mainly cytokines (e.g., Interleukin-2 (IL-2) and Interferon-.alpha. (INF-.alpha.)), activated mononuclear cells (e.g., lymphokine activated killer cells (LAK)) and antibodies. The BRMs act both directly on tumors and indirectly by enhancing non-specific or specific immunological and cytotoxic mechanisms.
To date, no substantial clinical success has been obtained using BRMs, mainly due to their toxicity and side effects. Active immunization against tumor cancer has also been proposed but found ineffective. Furthermore, several monoclonal antibodies (mAbs) were evaluated for use in diagnosis and therapy of cancer but no mAb has yet proven to be effective within a standard therapeutic procedure in cancer patients.
Various mAbs capable of binding to determinants on the surface of T cells have been found to induce proliferation, activation or differentiation of these cells.sup.(1). Binding of mAbs directed against the CD3/TCR complex on T cells.sup.(2-4), binding of mAbs directed at the CD2.sup.(5) receptor antigen on T cells as well as binding of both above kinds of antibodies to T cells, have been demonstrated to bring about T cell proliferation, IL-2 receptor expression and IL-2 production in T cells resulting in the enhancement of the cytolytic process in these cells. The anti CD3 mAb was shown to initiate an anti tumor activity in vivo in an animal model.sup.(6-7).
Various other mAbs directed against T-lymphocyte antigens have also been reported which, after binding to the cells, cause their activation such as mAbs directed against CD5.sup.(8), against CD69.sup.(9) and against CD28.sup.(10,11). Anti-CD28 mAbs were reported to have decreased the rate of growth of a murine melanoma although they were not successful in completely eliminating the tumors in the mice.sup.(12).
A mAb directed against a human B lymphoblastoid cell line termed "Daudi" was shown to stimulate murine lymphocytes and human peripheral T cells.sup.(13).